Increasing use is being made of paper substrates in the analysis and/or storage of biological materials. One such area of use concerns the growing need for rapid analysis of large quantities of blood samples in pharmacokinetic research, for example in drug discovery programmes. It is obviously desirable for such uses that the paper combines satisfactory mechanical properties with an ability to hold the biological material of interest in such a way that it can be subjected to analysis and/or further processing following storage. Examples of such papers are those known as FTA and FTA Elute (Whatman, part of GE Healthcare) described for example in U.S. Pat. Nos. 5,756,126 and 5,939,259. These papers have been impregnated with chemicals to provide cell lysis, preservation of nucleic acids and to facilitate further processing of nucleic acids.
However, these papers are specifically designed for nucleic acid analysis. There is also a strong interest in the use of paper substrates for processing of samples where proteins are analysed. Proteins differ from nucleic acids i.a. in that they are prone to denaturation and consequent loss of biological activity upon drying and storage. Proteins to be analysed, e.g. biomarkers or drugs in blood, are also often present in very low amounts and prone to masking by additives. In particular, analytical techniques such as mass spectroscopy and immunoassays can be affected by chemical additives. Plain untreated cellulose papers such as the 903 or 31ETF papers (Whatman, part of GE Healthcare) are used for preservation of blood samples followed by protein analysis, but do not always give the desirable analytical recoveries and biological activities of e.g. sensitive proteins. Addition of different fillers such as polyvinyl alcohol, Ficoll and sugars has been mentioned as a way to stabilize proteins in e.g. US2010/0209957 and WO2003/020924. These compositions are however also limited in the recoveries and activities of sensitive proteins.
In addition to stabilization for analytical purposes, there is also a need for stabilization of proteins and other sensitive biomolecules in therapeutic and diagnostic contexts, e.g. in storage of pharmaceutical formulations or diagnostic reagents in dry form.
Accordingly there is a need for sample preservation methods and sample preservation substrates with improved performance.